The blood platelet plays an important role in normal hemostasis and may be an important contributor to pathologic processes such as atherosclerosis. When the circulating platelet is stimulated, its surface membrane undergoes a series of as yet undefined changes permitting platelet aggregation. However, despite this change in surface character, stimulated platelets will not aggregate in the absence of intact fibrinogen. The goal of this study is to examine in detail the interaction between 125 I-labeled fibrinogen and the stimulated and non-stimulated human platelet in order to gain a better understanding of the mechanism of platelet aggregation. Human fibrinogen, freed of contaminating plasma proteins, will be radioiodinated and incubated with stimulated and non-stimulated platelets under varying conditions of time, pH and divalent cation concentration. Free and platelet-bound 125I-fibrinogen will be separated to determine the extent of fibrinogen binding to the platelet surface. Modifications of the fibrinogen molecule and of the platelet surface will be performed to further characterize the fibrinogen binding sites. In addition, study of fibrinogen binding to platelets with cogenitally abnormal membranes will be ndertaken. Since the platelet surface charge exerts a repulsive force between individual platelets, the effect of fibrinogen binding on platelet surface charge will be measured. Finally, attempts to isolate the platelet membrane fibrinogen binding site will be made using bifunctional crosslinking reagents and affinity chromatography.